Relacatib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Relacatib (SB-462795、GSK-462795) 是一种有效的口服生物可利用的小分子组织蛋白酶抑制剂，组织蛋白酶 K、L 和 V 的 Ki 值分别为 41、68 和 53 pM。

Relacatib (SB-462795, GSK-462795) is a potent and orally bioavailable small molecule cathepsin inhibitor with Ki of 41, 68 and 53 pM for cathepsin K, L and V, respectively; displays 39-300-fold selectivity over other cathepsins; inhibits endogenous cathepsin K in situ in human osteoclasts and human osteoclast-mediated bone resorption with IC50 of 45 nM and 70 nM, respectively; inhibits bone resorption both in vitro in human tissue and in vivo in cynomolgus monkeys.Osteoporosis Phase 2 Discontinued.

Relacatib are incubated with human osteoclastoma-derived osteoclasts seeded onto bovine cortical bone slices in vitro biological activity, it shows inhibitory potency with Ki values of 0.041 nM, 0.068 nM,0.063 nM,1.6 nM,and 13 nM against human cathepsin K, cathepsin L, cathepsin V, cathepsin S and cathepsin B, respectively in the assay. Relacatib is against Monkey cathepsin K, cathepsin L,cathepsin V and cathepsin B with Ki values of 0.041 nM, 0.28 nM, 0.72 nM and 11nM, respectively. Relacatib is against mouse cathepsin L and rat cathepsin L with Ki values of 0.20 nM and 0.17 nM, respectively.

Relacatib (1-2 mg/kg 0.5 h intravenous infusion; 2-4 mg/kg oral bolus gavage) exhibits T1/2, CL or Vdss with 109 mins, 19.5 mL/min/kg, or 1.86 L/kg in male Sprague-Dawley rats and 168 mins, 11.7 mL/min/kg, and 1.79 L/kg in monkeys, respectively in a PK iv/po crossover studies. The oral bioavailability of Relacatib is 28% in the monkey and 89.4% in the rats.SB-462795 (subcutaneous injection; 12 mg/kg; blood sample is drawn 1.5, 4, 24, 48, and 72 h post dose administration) significantly inhibits resorption as assessed by two markers of bone resorption,the N- (NTx) and C-telopeptides (CTx) of type I collagen measured in serum. SB-462795 does not exhibit difference of serum osteocalcin (a biomarker of osteoblast activity) between SB-462795 and vehicle treated animalsexcept for the 48 h time point where a significant reduction (42% lower than baseline vs. 18% lower than baseline with vehicle treatment). Animal Model:Cynomolgus monkey Dosage:12 mg/kg Administration:Subcutaneous injection; single dose; blood sample is drawn 1.5, 4, 24, 48, and 72 h post dose administrationResult:Was sufficiently high to significantly suppress bone resorption from 1.5 to 72 h post dosing.

SB-462795 | GSK-462795

Metabolic Enzyme/Protease

Cathepsin

Cathepsin

Metabolic Disease

Osteoporosis

362505-84-8

540.635

C27H32N4O6S

>98% (HPLC)

In Vitro:?DMSO : 40 mg/mL (73.99 mM)

O=C(C1=CC2=CC=CC=C2O1)N[C@@H](CC(C)C)C(N[C@@H]3C(CN(S(=O)(C4=NC=CC=C4)=O)[C@H](C)CC3)=O)=O

N-((S)-4-methyl-1-(((4S,7R)-7-methyl-3-oxo-1-(pyridin-2-ylsulfonyl)azepan-4-yl)amino)-1-oxopentan-2-yl)benzofuran-2-carboxamide

(-20℃)

With Ice Pack

≥ 2 years